Dysregulation of IL-10 production with aging: possible linkage to the age-associated decline in DHEA and its sulfated derivative.

Peripheral lymphoid cells isolated from the spleens and peritoneal cavities of aged mice were found to constitutively secrete the multifunctional cytokine interleukin (IL)-10 when cultured in vitro. B-Lymphocytes were implicated as the cell type responsible. Abnormal expression of this cytokine was also detected in vivo because high levels of mRNA for IL-10 were present in splenocytes freshly isolated from aged animals. In addition to the spontaneous secretion of IL-10, lymphoid cells from aged donors were hyperresponsive to exogenous stimulation with endotoxin, producing exaggerated quantities of both IL-10 and IL-6 in culture. Treatment of aged animals with dehydroepiandrosterone sulfate (DHEAS), a natural steroid, reversed the age-associated alterations in cytokine production, rendering the treated mice quite similar to mature adult controls. DHEAS treatment of aged mice also resulted in a lowering in the number of B1 cells present in the peritoneal cavity and also reduced the titers of circulating autoantibodies specific for phosphatidylcholine (PtC). Based on its wide range of biologic activities, a dysregulation in the mechanisms that control IL-10 production could be a major contributor to immunosenescence. The ability of DHEAS treatment to restore normal control over the expression of IL-10 may explain how this steroid enhances immunocompetence in aged animals.